Skip to main content
Log in

Clinical Pharmacokinetics of H1-Receptor Antagonists (The Antihistamines)

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

This article reviews clinical pharmacokinetic data on the H1-receptor antagonists, commonly referred to as the antihistamines. Despite their widespread use over an extendnd period, relatively little pharmacokinetic data are available for many of these drugs.

A number of H1-receptor antagonists have been assayed mainly using radioimmunoassay methods. These have also generally measured metabolites to greater or lesser extents. Thus, the interpretation of such data is complex. After oral administration of H1-receptor antagonists as syrup or tablet formulations, peak plasma concentrations are usually observed after 2 to 3 hours. Bioavailability has not been extensively studied, but is about 0.34 for chlorpheniramine, 0.40 to 0.60 for diphenhydramine, and about 0.25 for promethazine.

Most of these drugs are metabolised in the liver, this being very extensive in some instances (e.g. cyproheptadine and terfenadinej. Total body clearance in adults is generally in the range of 5 to 12 ml/min/kg (for astemizole, brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, promethazine and triprolidine), while their elimination half-lives range from about 3 hours to about 18 days [cinnarizine about 3 hours; diphenhydramine about 4 hours; promethazine 10 to 14 hours; chlorpheniramine 14 to 25 hours; hydroxyzine about 20 hours; brompheniramine about 25 hours; astemizole and its active metabolites about 7 to 20 days (after long term administration); flunarizine about 18 to 20 davs]. Thev also have relatively large apparent volumes of distribution in excess of 4 L/kg.

In children, the elimination half-lives of chlorpheniramine and hydroxyzine are shorter than in adults. In patients with alcohol-related liver disease, the elimination half-life of diphenhydramine was increased from 9 to 15 hours, while in patients with chronic renal disease that of chlorpheniramine was very greatly prolonged. Little, if any, published information is available on the pharmacokinetics of these drugs in neonates, pregnancy or during lactation.

The relatively long half-lives of a number of the older H1-receptor antagonists such as brompheniramine, chlorpheniramine and hydroxyzine suggest that they can be administered to adults once daily.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aberncthy, D.R. and Greenblatl, D.J.: Diphcnhydramine determination in human plasma by gas-liquid chromatography using nitrogen-phosphorous detection: Application to single lowdose pharmacokinetic studies. Journal of Pharmaceutical Sciences 72: 941–943 (1983).

    Article  Google Scholar 

  • Albert, K.S.. Hallmark, M.R.: Sakmar, E.: Wcidler, D.J. and Wagner, J.G.: Pharmacokinetics of diphenhydramine in man. Journal of Pharmacokinetics and Biopharmaccutics 3: 159–170 (1975).

    Article  CAS  Google Scholar 

  • Ali, H.M. and Beckett, A.H.: Rapid method for the determination of chlorpheniramine in urine. Journal of Chromatography 223: 208–212 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Athanikar, N.K.: Peng, G.W.: Nation, R.L.: Huang, S.-M. and Chiou, W.L.: Chlorpheniramine. I. Rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine by high-performance liquid chromatography. Journal of Chromatography 162: 367–376 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Barnhart, J.W. and Johnson, J.D.: Simplified gas-chromatographic method for the determination of chlorpheniramine in serum. Analytical Chemistry 49: 1085–1086 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Baugh, R. and Calvert, R.T.: A rapid method for the determination of diphenhydramine in plasma. British Journal of Clinical Pharmacology 3: 1062–1064 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Beckett, A.H. and Wilkinson, G.T.: Influence of urine pH and flow rate on the renal excretion of chlorpheniramine in man. Journal of Pharmacy and Pharmacology 17: 256–257 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Bellinger, W.G.: Goldbert, M.J.: Spector, R.: Chiang, C-K. and Ghoneim, M.M.: Diphenhydramine: Kinetics and psychomotor effects in elderly women. Clinical Pharmacology and Therapeutics 32: 387–391 (1982).

    Article  Google Scholar 

  • Biber, W.: Gundcrt-Remy, U. and Weber, E.: Relationship between antihistamine activity and plasma level of diphenydramine. European Journal of Clinical Pharmacology 7: 393–395 (1974).

    Article  Google Scholar 

  • Bruce, R.B.: Turnbull, L.B.: Newman, J.H. and Pilts, J.E.: Metabolism of brompheniramine. Journal of Medicinal Chemistry 11: 1031–1034 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Carruthers, S.G.: Shocman, D.W.: Hignite, C.E. and Azarnoff, D.L.: Correlation between plasma diphenhydramine level and sedative and anti-histamine effects. Clinical Pharmacology and Therapeutics 23: 375–382 (1978).

    PubMed  CAS  Google Scholar 

  • Casy, A.F.: Chemistry of anti-Hi histamine antagonists: in Rocha and Silva (Eds) Histamine II and Anti-histamines. Chemistry. Metabolism and Physiological and Pharmacological Actions. Handbook of Experimental Pharmacology. Vol. 18. Part 2. pp. 93–108 (Springer Verlag, Berlin 1978).

    Google Scholar 

  • Chang, T.: Okcrholm, R.A. and Glazo, A.J.: Identification of diphenhydramine (Benadryl) metabolites in human subjects. Research Communications in Chemical Pathology and Pharmacology 9: 391–404 (1974).

    PubMed  CAS  Google Scholar 

  • Chaudhuri, N.K.: Sevando, O.A.: Manniello, M.J.: Luders, R.C.. Chao, D.K. and Bartlett, M.F.: Metabolism of tripelcnnamine in man. Drug Metabolism and Disposition 4: 372–378 (1976).

    PubMed  CAS  Google Scholar 

  • Cook, C.E.: Williams, D.L.: Myers, M.: Tallent, C.R.: Lecson, G.A. et al.: Radioimmunoassay for terfenadine in human plasma. Journal of Pharmaceutical Sciences 69: 1419–1422 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Davies, B.H. and Rocchiccioli, K.: Oxatomidc plasma levels in man during chronic dosing. Pharmalherapeutica 3: 365–369 (1983).

    CAS  Google Scholar 

  • DeAngelis, R.L.: Kearney, M.F. and Welch, R.M.: Determination of triprolidine in human plasma by quantitative TLC. Journal of Pharmacuctical Sciences 66: 841–843 (1977).

    Article  CAS  Google Scholar 

  • DiGregorio, G.J. and Ruch, E.: Human whole blood and parotid saliva concentrations of oral and intramuscular promethazine. Journal of Pharmaceutical Sciences 69: 1457–1459 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Douglas, W.W.: Histamine and 5-hydroxytryptamine (serotonin) and their antagonists: in Gilman et al, (Eds) The Pharmacological Basis of Therapeutics. 6th ed.. pp. 609–646 (MacMillan, New York 1980).

    Google Scholar 

  • Dube, L.M.: Bloch, R.: Warner, R.N.: Hyslop, R.M.: Popovich, N.G. and Gonzalez, M.A. Pharmacokinetics of chlorpheniramine in chronic renal failure: Effect of hemodialysis and peritoneal dialysis. American Pharmaceutical Association 127th Annual Meeting (Abstract No. 46) 10: 84 (1980).

    Google Scholar 

  • Findlay, J.W.A.: Rutz, R.F.: Sailstad, J.M.: Warren, J.T. and Welch, R.M.: Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers. British Journal of Clinical Pharmacology 18: 901–906 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Flor, S.C.: Determination of the calcium antagonist flunarizine in biological fluids by gas-liquid chromatography. Journal of Chromatography 272: 315–323 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Gartciz, DA.: Hook, R.H.: Walker, B.J. and Okcrholm, R.A.: Pharmacokinetics and biotransformation studies of terfenadine in man. Arzneimittel-Forschung 32: 1185–1190 (1982).

    Google Scholar 

  • Graham, G. and Boll, A.G.: Half-life of diphcnylpyraline in man. Journal of Pharmacokinetics and Biopharmacuetics 2: 191–195 (1974).

    CAS  Google Scholar 

  • Heykants, J.: Pharmacokinetics and metabolism of astcmizole in man; in Astcmizole: A New Non-Sedative. Long-Acting H1 Antagonist pp. 25–34 (Medical Education Services, Oxford 1984).

    Google Scholar 

  • Heykants, J.: DeCrec, J. and Horig, C.: Steady-state plasma levels of flunarizine in chronically treated patients. Arzneimittel-Forschung 29: 1168–1171 (1979).

    PubMed  CAS  Google Scholar 

  • Heykants. J.: Geuens. I.: Wocstcnborghs. R.: Dony. J.: Scheygrond. H. and Amery, W.: Biocquivalcnce of two oxatomide formulations (a 30mg tablet and a 25 mg/ml suspension) in a group of seven healthy subjects. Janssen Pharmaceutica Clinical Research Report R35443/27 (1981).

  • Heykants. J.: Hendriks. R.: Michicls. M. and Scheygrond. H.: Relative bioavailability in five volunteers of three oxalomide formulations in comparison to a drug solution. Janssen Pharmacuetica Clinical Rescarch Report R35443/17 (1978).

  • Hcykants. J.: Michielson. L.: Lorreyne. W.: Wocstenborghs, R.: Scheygrond. H. and Ryntjcns. A.: Biocquivalcnce study of two flunarizine formulations (a 5mg capsule and a 10mg tablet) in a group of six healthy subjects. Janssen Pharmaceulica Clinical Research Report R14950/52 (1981).

  • Hcykants, J. and Vanden Bussche. G.: On the pharmacokinctics nfasicmizolc in volunteers and patients. Janssen Pharmaceu-tica Clinical Research Report R435I2/62 (1983).

  • Hcykanls. J. and Van Peer. A.: Steady-state pharmacokinetics of flunarizine in man arc predictable from single-dose kinetics. Janssen Pharmaceutica Clinical Research Report R14950/58 (1983).

  • Hintze, K.L.: Wold, J.S. and Fischer, L.J.: Disposition of cyproheptadine in rats, mice and humans and identification of a stable epoxide-metabolite. Drug Metabolism and Disposition 3: 1–9 (1975).

    PubMed  CAS  Google Scholar 

  • Holmes, Brogden, R.N.: Heel, R.C.: Speight, T.M. and Avery, O.S.: Flunarizinc: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 27: 6–44 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Howarth, P.H.: Emmanuel, M.B. and Holgate, S.T.: Astemizole, a potent histamine H1-receptor antagonist: Effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin wheal responses and relationship to serum levels. British Journal of Clinical Pharmacology 18: 1–8 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Huang, S-M.: Athanikar, N.K.: Sridhar, K.: Huang, Y.C. and Chiou, W.L.: Pharmacokinetics of chlorpheniramine after oral and intravenous administration in normal subjects. European Journal of Clinical Pharmacology 22: 359–365 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Kabasakalian, P.: Taggart, M. and Townley, E.: Urinary excretion of pheniramine and its N-demethylated metabolites in man — comparison with chlorpheniramine and brompheniramine data. Journal of Pharmaceutical Sciences 57: 621–623 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, K.A.: Halmi, K.A. and Fischer, L.J.: Urinary excretion of a quaternary-ammonium glucuronide metabolite of cyproheptadine in humans undergoing chronic drug therapy. Life Sciences 21: 1813–1820 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Kohlhof, K.J.: Stamp, D. and Ziggamia, J. A.: Analysis of doxylaminc in plasma by high-performance liquid chromatography. Journal of Pharmaceutical Sciences 72: 961–962 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Kok, T.H.H.G.: Taitz, L.S.: Bennett, M.J. and Holt, D.W.: Drowsiness due to clemastine transmitted in breast milk. Lancet 1: 914–915 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Kotzan, J.A.: Valiner, J.J.: Stewart, J.T.: Brown, W.J.: Viswanathan, C.T. et al.: Bioavailability of regular and controlled-releasc chlorpheniramine products. Journal of Pharmaceutical Sciences 71: 919–923 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Kuntzman, R.: Klutch, A.: Tsai, I. and Burns, J.J.: Physiological distribution and metabolic inactivalion of chlorcyclizine and cyclizinc. Journal of Pharmacology and Experimental Therapeutics 149: 29–35 (1965).

    PubMed  CAS  Google Scholar 

  • Kuntzman, R.: Tsai, I. and Burns, J.J.: Importance of tissue and plasma binding in determining the retention of norchlorcyclizine and norcyclizine in man, dog and rat. Journal of Pharmacology and Experimental Therapeutics 158: 332–339 (1967).

    PubMed  CAS  Google Scholar 

  • Lai, Stoll, R.G.: Look, Z.M. and Yacobi, A.: Urinary excretion of chlorpheniramine and pseudoephedrinc in humans. Journal of Pharmaceutical Sciences 68: 1243–1246 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Land, G.: Dean, K. and Bye, A.: Determination of cyclizinc and norcyclizine in plasma and urine using gas-liquid chromatography and nitrogen selective detection. Journal of Chromatography 222: 135–140 (1981).

    Article  PubMed  CAS  Google Scholar 

  • La-son, G.A.: Chan, K.Y.: Knapp, W.C.: Biebenbach, S.A.: Wright, G.J. and Okcrholm, R.A.: Metabolic disposition of terfenadine in laboratory animals. Arzneimittel-Forschung 32: 1173–1178 (1982).

    Google Scholar 

  • Lin, C.: Lim, J. and Symchowicz, S.: Bioavailability of d-pseu doephedrinc and azaladinc from a repeat action tablet formulation. Journal of International Medical Research 10: 122–125 (1982).

    PubMed  CAS  Google Scholar 

  • Meredith, C.G.: Christian, C.D.: Johnson, R.F.. Madhavan, S.V. and Schenker, S.: Diphenhydramine disposition in chronic liver disease. Clinical Pharmacology and Therapeutics 35: 474–479 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Meuldermans, W.: Hendricks, J.: Harkmans, R.: Swysen, E.: Woestcnborghs, R. et al.: Excretion and metabolism of flunarizine in rats and dogs. Arzncimittel-Forschung 33: 1142–1151 (1983).

    CAS  Google Scholar 

  • Meuldermans, W.: Hendricks, J.: Knaeps, F.: Lauwers, W.: Heykants, J. and Grindel, J.M.: Plasma levels, biotransformation and excretion of oxatomidc(R35 443) in rats, dogs and man. Xenobiotica 14: 445–462 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Michicls, M.: Hendriks, R.: Knaeps, F.: Woestenborghs, R. and Hcykams, J.: Absorption and tissue distribution of flunarizine in rats, pigs and dogs. Arzneimittel-Forschung 33: 1135–1142 (1983).

    Google Scholar 

  • Michicls. M.: Hendricks, R.: Prinsen, P. and Heykants. J.: Radioimmunoassay for oxatomide: Improvement of specificity Janssen Pharamceutica Clinical Research Report (R35 443/28) (1978).

  • Moolenaar, F.: Ensing, J.G.: Bolhuis, B.G. and Visser, J.: Absorption rate and bioavailability of promethazine from rectal and oral dosage forms. International Journal of Pharmaceutics 9: 353–357 (1981).

    Article  CAS  Google Scholar 

  • Morrison, P.J.: Bradbrook, I.D. and Rogers, H.J.: Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas-liquid chromatography. British Journal of Clinical Pharmacology 7: 349–352 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Nauta, W.T. and Rekker, R.F.: Structure-activity relationships of H1-receptor antagonists: in Rocha and Silva (Ed.) Histamine 11 and Anti-histamines: Chemistry. Metabolism and Physiological and Pharmacological Actions. Handbook of Experimental Pharmacology. Vol. 18. Part 2. (Springer-Verlag, Berlin 1978).

    Google Scholar 

  • Nitsche, V. and Mascher, H.: Rapid high-performance liquid Chromatographie assay of cinnarizine in human plasma. Journal of Chromatography 227: 521–525 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Okerholm, R.A.: Weiner, D.L.: Hook, R.H.: Walker, B.J.: Leeson, G.A. et al.: Bioavailability of terfenadine in man. Biopharmacculics and Drug Disposition 2: 185–190 (1981).

    Article  CAS  Google Scholar 

  • Paton. D.M.: Receptors for histamine; in Schacter (Ed.) Histamine and Anti-histamines. International Encyclopedia of Pharmacology and Therapeutics. Section 74. Vol. I. pp. 3–24 (1972).

  • Peets, E.A.: Jackson, M. and Symchowicz, S.: Metabolism of chlorpheniramine maleate in man. Journal of Pharmacology and Experimental Therapeutics 180: 464–472 (1972).

    CAS  Google Scholar 

  • Perkins, J.G.: Bressler, R.: Heatherington, D.: Cato, A. and Dickerson, J.: A bioavailability and safety study comparing Actifed sustained-action (SA) capsules to Actifed immediate-release (IR) tablets. Current Therapeutic Research 28: 650–668 (1980).

    Google Scholar 

  • Porter, C.C.: Arisen, B.H.: Gruber, V.F.: Titus, D.C. and Vandcnhcuvel, W.J.A.: Human metabolism of cyproheptadine. Drug Metabolism and Disposition 3: 189–197 (1975).

    PubMed  CAS  Google Scholar 

  • Puitemans, M.: Bogacrt, M.: Hoogewijs, G.: Dryon, L.: Massart, D.L. and Vanhaclsl, L.: Determination of cinnarizine in whole blood and plasma by reversed phase HPLC. and its application to a pharmacokinctic study. Journal of Liquid Chromatography 7: 2237–2251 (1984).

    Article  Google Scholar 

  • Quinn, J. and Calverl, R.: The disposition of promethazine in man. Journal of Pharmacy and Pharmacology 28: 59P (1976).

    Google Scholar 

  • Richards, D.M.: Brogden, R.N.: Heel, R.C.: Speight, T.M. and Avery, G.S.: Astemizole: A review of its pharmacodynamic properties and therapeutic efficacy. Drugs 28: 38–61 (1984a).

    Article  PubMed  CAS  Google Scholar 

  • Richards, D.M.: Brogden, R.N.: Heel, R.C.: Speight, T.M. and Avery, G.S.: Oxatomidc: A review of its pharmacodynamic properties and therapeutic efficacy. Drugs 27: 210–231 (1984b).

    Article  PubMed  CAS  Google Scholar 

  • Rumore, M.M.: Clinical pharmacokinetics of chlorpheniramine. Drug Intelligence and Clinical Pharmacy 18: 701–707 (1984).

    PubMed  CAS  Google Scholar 

  • Sanders, S.W.: Warner, R.N.: Geogitis, J.W.: Eigen, H. and Gonzalez, M.A.: Dexchlorphcniramine disposition in man. American Pharmaceutical Association Journal 10: 84 (1980).

    Google Scholar 

  • Schwinghammer, T.L.: Juhl, R.P.: Dittcrt, L.W.: Mclechil, S.K.: Kroboth, F.J. and Chungi, V.S.: Comparison of the bioavailability of oral, rectal and intramuscular promethazine. Biopharmaceutics and Drug Disposition 5: 185–194 (1984).

    Article  CAS  Google Scholar 

  • Simons, F.E.R.: Frith, E.M. and Simons, K.J.: The pharmacokinetics and antihistamine effects of brompheniramine. Journal of Allergy and Clinical Immunology 70: 458–464 (1982a).

    Article  PubMed  CAS  Google Scholar 

  • Simons, F.E.R.: Luciuk, G.H. and Simons, K.J.: Pharmacokinetics and efficacy of chlorpheniramine in children. Journal of Allergy and Clinical Immunology 69: 376–381 (1982b).

    Article  PubMed  CAS  Google Scholar 

  • Simons, F.E.R.: Simons, K.J.: Becker, A.N. and Haydey, R.P.: Pharmacokinetics and antipruritic effects of hydroxyzine in children with atopic dermatitis. Journal of Paediatrics 104: 123–127 (1984a).

    Article  CAS  Google Scholar 

  • Simons. F.E.R.: Simons. K.J. and Frith. E.M.: The pharmacokinetics and antihistamine effects of the H-1 receptor antagonist hydroxyzine. Journal of Allergy and Clinical Immunology (In press 1984b).

  • Simons, K.J.: Simons, F.E.R.: Luciuk, G.H. and Frith, E.M.: Urinary excretion of chlorpheniramine and its metabolites in children. Journal of Pharmaceutical Sciences 73: 595–599 (1984c).

    Article  PubMed  CAS  Google Scholar 

  • Sorkin, E.M. and Heel, R.C.: Terfenadine: A review of its pharmacodynamic properties and therapeutic efficacy. Drugs 29: 34–56 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Spector, R.. Choudhury, A.K.: Chiang, C-K.: Goldberg, M.J. and Ghoneim, M.M.: Diphenhydramine in Orientals and Caucasians. Clinical Pharmacology and Therapeutics 28: 229–234 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Taylor, Ci.: Calvert, R.T. and Houston, J. Determination of promethazine in biological fluids. Analytical Letters 12: 1435–1442 (1979).

    Article  CAS  Google Scholar 

  • Taylor, G. and Houston, J. Simultaneous determination of promethazine and two of its circulating metabolites by highperformance liquid chromatography. Journal of Chromatography 230: 194–198 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Taylor, Ci. and Houston, J. Determinants of systemic availability of promethazine in rabbits. Journal of Pharmacy and Pharmacology 35: 284–288 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Taylor, G.: Houston, J.B.: Shaffer, J. and Mower, G.: Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man. British Journal of Clinical Pharmacology 15: 287–293 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Tham, R.: Norlandcr, Hagermark, O. and Fransson, L.: Gaschromalography of clemastine. A study of plasma kinetics and biological effect. Arzncimittel-Forschung 28: 1017–1020 (1978).

    CAS  Google Scholar 

  • Thompson, J.A.: Bloedow, D.C. and Leffert, F.H.: Pharmacokinetics of intravenous chlorpheniramine in children. Journal of Pharmaceutical Sciences 70: 1284–1286 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Thompson, J.A. and Leffert, F.H.: Sensitive GLC-mass spectrometric determination of chlorpheniramine in serum. Journal of Pharmaceutical Sciences 69: 707–710 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Vallner, J.J.: Kotzan, J.A.: Stewart, J.T.: Brown, W.J.: Honigberg, I.L. el al.: Blood levels following multiple oral dosing of chlorpheniramine conventional and controlled release preparations. Biopharmaceutics and Drug Disposition 3: 95–104 (1982).

    Article  CAS  Google Scholar 

  • chlorpheniramine to seven subjects. Current Therapeutic Research 26: 449-453 (1979).

    Google Scholar 

  • Van Landcghem, V.H.: Burke, J.T. and Thcbaull, J.: The use of a human bioassay in determining the biocquivalcnce of two formulations of the antihistamine icrfenadine. Clinical Pharmacology and Therapeutics 27: 290–291 (1980).

    Google Scholar 

  • Woeslenborghs, R.. Embrechts, L. and Heykants, J.: Simultaneous determination of astemizote and its demethylated metabolite in animal plasma and tissues by high-performance liquid chromatography. Journal of Chromatography 278: 359–366 (1983).

    Article  Google Scholar 

  • Woeslenborghs, R.: Michielsen, L; Lorrcyne, W. and Heykants, J.: Sensitive gas chromatographic method for the determination of cinnarizine and flunarizine in biological samples. Journal of Chromatography 232: 85–91 (1982).

    Article  Google Scholar 

  • Wold, J.S. and Fischer, L.J.: The tissue distribution of cyproheptadine and its metabolites in rats and mice. Journal of Pharmacology and Experimental Therapeutics 183: 188–196 (1972).

    PubMed  CAS  Google Scholar 

  • Woodward, J.K. and Munro, N.L.: Terfenadine, the first nonsedating antihistamine. Arzneimiltcl-Forschung 32: 1154–1156 (1982).

    CAS  Google Scholar 

  • Vacobi, A.: Stolt, R.G.: Chao, G.C.: Carter, J.E.: Baaske, D.M. et al.: Evaluation of sustained-action chlorpheniraminc-pscudocphedrine dosage forms in humans. Journal of Pharmaceutical Sciences 69: 1077–1081 (1980).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paton, D.M., Webster, D.R. Clinical Pharmacokinetics of H1-Receptor Antagonists (The Antihistamines). Clin Pharmacokinet 10, 477–497 (1985). https://doi.org/10.2165/00003088-198510060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198510060-00002

Keywords

Navigation